Brain Research最新文献

{"title":"Cannabidiol reverses microglia activation and loss of parvalbumin interneurons and perineuronal nets in a mouse model of schizophrenia.","authors":"Naielly Rodrigues da Silva, Davide Gobbo, Felipe V Gomes, Anja Scheller, Frank Kirchhoff, Elaine Del Bel, Francisco Silveira Guimarães","doi":"10.1016/j.brainres.2025.149772","DOIUrl":"https://doi.org/10.1016/j.brainres.2025.149772","url":null,"abstract":"<p><p>Cannabidiol (CBD) has shown potential for treating schizophrenia (SCZ) by targeting its positive and negative cognitive symptoms. In this study, we investigated if CBD could reverse the memory impairment observed after chronic administration of the NMDA receptor antagonist MK-801. Chronic treatment with MK-801 (0.5 mg/kg i.p., twice a day, for 14 days) resulted in short- and long-term memory deficits and decreased relative power of γ oscillations in freely moving animals. CBD administration (30 mg/kg i.p. daily for seven days after the MK-801 treatment period) reversed these changes. The cognitive effects of CBD were prevented by blocking 5-HT1A but not CB2 receptors. At the cellular level, the depletion of parvalbumin-positive neurons and their associated perineuronal nets in the prelimbic medial prefrontal cortex (mPFC) and ventral hippocampus (vHip) induced by MK-801 was reversed by CBD. This neuroprotective effect was mediated by 5-HT1A and CB2 receptors in the vHip but was independent of these receptors in the mPFC. Additionally, CBD reversed MK-801-induced microglial activation in both mPFC and vHip, again through 5-HT1A and CB2 receptors. These findings suggest that CBD modulates multiple pathways affected in SCZ-like conditions, offering a promising therapeutic avenue for SCZ treatment.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149772"},"PeriodicalIF":2.7,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ononin modulates SIRT2-mediated glycolysis and inflammation in LPS-activated microglia via PKM2 deacetylation.","authors":"Qunshan Chen, Weixian Xu, Xiaofang Tong, Mei Cheng","doi":"10.1016/j.brainres.2025.149763","DOIUrl":"https://doi.org/10.1016/j.brainres.2025.149763","url":null,"abstract":"<p><strong>Background: </strong>Inhibition of inflammation and glycolysis of microglia contributes to neuropathic pain treatment. Ononin, a compound isolated from various plants, has been found to have various anti-inflammatory and anti-tumor effects.</p><p><strong>Aim: </strong>To investigate the the therapeutic potential and mechanism of Ononin on microglial activation.</p><p><strong>Methods: </strong>BV2 microglial cells were treated with LPS to mimic microenvironment of neuropathic pain in vitro, and gene expression was analyzed by qPCR array analysis after Ononin treatment. The effects of Ononin and SIRT2 gene on inflammation and glycolysis were then investigated. PKM2 acetylation sites were predicted using the GPS-PAL database. The interaction between PKM2 and SIRT2 protein was also studied.</p><p><strong>Results: </strong>Ononin at 40 μM significantly inhibited inflammation and glycolysis in LPS-treated BV2 microglial cells, and this was related to the upregulation of SIRT2 levels. Inhibition of SIRT2 weakened the regulatory effects of Ononin, and induced PKM2 acetylation to enhance glycolysis in BV2 cells. SIRT2 exerts deacetylation modification at K207 site of PKM2 protein to reduce the stability of PKM2 protein.</p><p><strong>Conclusions: </strong>SIRT2-mediated metabolic reprogramming and inflammation are critical for neuropathic pain, and Ononin shows therapeutic potential by modulating SIRT2 to suppress PKM2 protein stability in the deacetylation way, suggesting it as a promising treatment option.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149763"},"PeriodicalIF":2.7,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Role of dexmedetomidine in postoperative cognitive dysfunction and sleep improvement in aged rats by regulating the PI3K/Akt signaling pathway and its mechanism” [Brain Res. 1852 (2025) 149482]","authors":"Ying Kong ,&nbsp;Xiaopeng Wang ,&nbsp;Jun Pang ,&nbsp;Haiyan Huo ,&nbsp;Xiaofang Wang","doi":"10.1016/j.brainres.2025.149722","DOIUrl":"10.1016/j.brainres.2025.149722","url":null,"abstract":"","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1863 ","pages":"Article 149722"},"PeriodicalIF":2.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144204815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corticosteroid-induced gene expression is attenuated in the hippocampus of mice with model of post-traumatic stress disorder","authors":"Roman Vasyl ,&nbsp;Bohdan Haran ,&nbsp;Tetiana Lahuta ,&nbsp;Israel Liberzon ,&nbsp;Victor Dosenko","doi":"10.1016/j.brainres.2025.149760","DOIUrl":"10.1016/j.brainres.2025.149760","url":null,"abstract":"<div><div>One of the distinctive features of post-traumatic stress disorder (PTSD) is an impairment of the hypothalamic–pituitary–adrenal (HPA) axis. Increased inhibition of cortisol synthesis after dexamethasone administration in patients indicates hyperactivation of the HPA feedback loop. This phenomenon may be explained by increased sensitivity of hypothalamic CRH-producing neurons to corticosteroids. Since corticosteroids signaling influences memory processing mechanisms, the issue of hippocampal glucocorticoid (GR) and mineralocorticoid (MR) receptors sensitivity is important for the pathogenesis of PTSD. Expression of both GR and MR target genes (<em>Mt2</em>, <em>Fkbp5</em>, and <em>Jdp2</em>) mRNA in hippocampal tissue of experimental mice was measured using RT-qPCR. The single prolonged stress (SPS) paradigm was used as an animal PTSD model. We found an attenuated expression of the GR negative regulator – co-chaperone <em>Fkbp5</em> in animals after SPS exposure. When large doses of dexamethasone (5 <!--> <!-->mg/kg) or hydrocortisone (10 <!--> <!-->mg/kg) were administered, the expression of <em>Mt2</em> and <em>Fkbp5</em> increased in control mice, but not in the SPS group. There were no significant changes in <em>Crh</em> expression detected in all mice groups. This indicates lower transcriptional reactivity of GR, but not MR, in mice with the PTSD model, compared to the control group. Thus, our findings provide a new insight into the understanding of brain GR signaling in PTSD.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1863 ","pages":"Article 149760"},"PeriodicalIF":2.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144231342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytomegalovirus: An undervalued biological parameter of cognition in schizophrenia","authors":"Zifan You,&nbsp;Liangliang Wang,&nbsp;Shanshan Chen,&nbsp;Luyao Zou,&nbsp;Jinsong Tang","doi":"10.1016/j.brainres.2025.149719","DOIUrl":"10.1016/j.brainres.2025.149719","url":null,"abstract":"<div><div>There is growing evidence that the brain is not an immune-privileged area, with central nervous system (CNS) cells being susceptible to inflammation as the brain responds to infection. Among the myriad of pathogens capable of infiltrating the neural environment, cytomegalovirus (CMV) has been one of the most extensively studied. Notably, CMV has been implicated in a range of neuropsychiatric disorders, including schizophrenia (SCZ). The objective of this review is to provide a comprehensive analysis of the impact of CMV on cognitive function in SCZ. Our review covers studies that explore the intersection of SCZ and CMV infection, thus establishing a theoretical framework for understanding the cognitive deficits associated with CMV. Recent findings regarding the SCZ-CMV relationship include: (1) the association of CMV with cognitive impairment, (2) CMV-related neuropathology and neuroimaging findings linked to the pathogenesis of cognitive deficits, and (3) therapeutic interventions for CMV in vivo. Given that no prior studies have explored the causal relationship between CMV biomarkers and cognitive features in SCZ, we have employed Mendelian randomization (MR) analysis to further investigate these associations. Through this review, we aim to offer new insights into the pathogenesis, diagnosis, treatment, and prognosis of SCZ by exploring the relationship between CMV and SCZ.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1863 ","pages":"Article 149719"},"PeriodicalIF":2.7,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mostuea batesii Baker (Gelsemiaceae) root bark hydroethanolic extract unveil neuroprotective, antihypertensive, and antioxidant activities in rat model exposed to lead acetate","authors":"Jean Victor Harold Akono ,&nbsp;Rigobert-Espoir Ayissi Mbomo ,&nbsp;Adjia Hamadjida ,&nbsp;Elisabeth Sylvie Ngoa Manga ,&nbsp;Eric Bila Guemekane ,&nbsp;Josepha Laure Mbassi Eyebe ,&nbsp;Rodrigue Fifen ,&nbsp;Yannick Carlos Tcheuchoua ,&nbsp;Laurette Calixte Nga Ngono ,&nbsp;Théophile Dimo","doi":"10.1016/j.brainres.2025.149759","DOIUrl":"10.1016/j.brainres.2025.149759","url":null,"abstract":"<div><div>Lead poisoning is the first occupational disease in the Eastern region of Cameroon and is associated with mining activities. It has serious neurological and cardiovascular consequences that can lead to death. Conventional treatments available do not significantly reduce the bioavailability of lead in blood and are not accessible to everyone. Therefore, the purpose of this study is to investigate the neuroprotective and antihypertensive effects of <em>Mostuea batesii</em> (<em>M. batesii</em>) extract in a rat model of lead acetate poisoning. Forty-eight rats were divided into six groups (n = 8) and received in addition to lead acetate at 50 <span><span>mg.kg</span><svg><path></path></svg></span>⁻¹, the following treatments for 28 days except the normal group: distillated water (Negative), a mixture of imipramine and Losartan (10/50 <span><span>mg.kg</span><svg><path></path></svg></span>⁻¹) (positive), and <em>Mostuea batesii</em> extract at doses of 100, 200, and 300 <span><span>mg.kg</span><svg><path></path></svg></span>⁻¹. The normal group was treated with distillated water without Lead acetate. Following a behavioral investigation, hemodynamic parameters were measured, and the sacrifice was performed. Blood and organs including cerebral cortex, hippocampus, aorta, and liver, were obtained for biochemical and histological examinations. Lead acetate at 50 mg.kg⁻¹ showed an increase of immobility time in the forced swimming test, as well as the heart rate (13.65 %), atherogenic index, (p &lt; 0.001). Moreover, lead acetate induced oxidative stress by increasing MDA and Nitrogen oxide levels in prefrontal cortex and hippocampus, as well as neuronal loss, (p &lt; 0.001) in CA3 by to cytolysis, and pycnosis. Treatment with <em>Mostuea batesii</em> at doses of 100 and 200 mg/kg on the other hand restored these parametters by increasing GSH levels, reducing the concentration of MDA and Nitrogen oxide and restoration of hippocampal cells microarchitecture. Moreover, <em>M. batesii</em> extract has significally reduce systolic blood pressure comparative by the negative group, as well as heart rate and the aorta thickness. This extract is thought to have neuroprotective, antihypertensive, and antioxidant properties.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1864 ","pages":"Article 149759"},"PeriodicalIF":2.7,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corticotropin-releasing hormone neurons in the central Amygdala: An integrative hub for pain, emotion, and addiction neurobiology","authors":"Jia Li ,&nbsp;Zi-Ang Li ,&nbsp;Hui-Min Tian ,&nbsp;Sha-Sha Tao ,&nbsp;Qian Zhang ,&nbsp;Fei Li ,&nbsp;Yun-Qing Li","doi":"10.1016/j.brainres.2025.149753","DOIUrl":"10.1016/j.brainres.2025.149753","url":null,"abstract":"<div><div>The central amygdala (CeA) is a critical node within the limbic system. Corticotropin-releasing hormone-positive (CRH⁺) neurons within the CeA are essential for modulating stress responses and negative emotional behaviors. Recent investigations on CRH⁺ neurons in CeA have elucidated their multifaceted and significant biological roles in physiological regulation, encompassing pain, negative emotion, fear memory, and drug withdrawal. This review seeks to provide a comprehensive analysis of the neuronal subtypes and their distribution within the CeA, the afferent and efferent connectivity of of CRH⁺ neurons in the CeA, and their associated functional roles, thereby providing insights and a framework for future research.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1863 ","pages":"Article 149753"},"PeriodicalIF":2.7,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between epigenetic mark 5-hydroxymethylcytosine and brain pathophysiology","authors":"Amandeep Kaur Kang ,&nbsp;Uma Dhawan ,&nbsp;Birendra Nath Mallick","doi":"10.1016/j.brainres.2025.149755","DOIUrl":"10.1016/j.brainres.2025.149755","url":null,"abstract":"<div><div>Over the last decade, the identification of the sixth base, 5-hydroxymethylcytosine (5-hmC), and its emerging association with brain disorders have provided new insights into the pathophysiological implications of neuroepigenetic changes. This epigenetic modification occurs due to Ten-eleven translocase 1/2/3 (Tet1/2/3) mediated oxidation of 5-methylcytosine (5-mC) molecules, reversing the methyl-dependent silencing of genes and changing the genomic landscape within the cells, thereby altering downstream signaling cascades. 5-hmC is enriched in the brain tissues and is involved in neurogenesis and brain development. However, the exact functional significance of 5-hmC has not been fully explored. The level of 5-hmC is altered with age, environmental toxicity, hormonal imbalances, exposure to challenges like sleep loss, changes in the level of neurotransmitters, and mutations in the Tet enzymes, resulting in the onset, sensitization or predisposition to brain pathology. In this review, we have discussed the recent studies investigating the role of DNA hydroxymethylation in various neurological disorders. These findings suggest that 5-hmC may play a regulatory role in the aetiology of neurodevelopmental, neurodegenerative and neuropsychiatric disorders. We also propose a potential role of 5-hmC in neuronal disorders associated with REM sleep deprivation.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1863 ","pages":"Article 149755"},"PeriodicalIF":2.7,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144221753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spearmint extract Neumentix downregulates amyloid-β accumulation by promoting phagocytosis in APP23 mice","authors":"Xinran Hu ,&nbsp;Ryuta Morihara ,&nbsp;Yusuke Fukui ,&nbsp;Yuting Bian ,&nbsp;Hongming Sun ,&nbsp;Ricardo Satoshi Ota-Elliott ,&nbsp;Hiroyuki Ishiura ,&nbsp;Koji Abe ,&nbsp;Toru Yamashita","doi":"10.1016/j.brainres.2025.149752","DOIUrl":"10.1016/j.brainres.2025.149752","url":null,"abstract":"<div><div>In recent years, many researchers have focused on natural compounds that can effectively delay symptoms of Alzheimer’s disease (AD). The spearmint extract Neumentix, which is rich in phenolic compounds, has been shown to reduce inflammatory responses and oxidative stress in mice. However, the effect of Neumentix on AD has not been thoroughly studied. In this study, APP23 transgenic female and male mice were administered Neumentix orally from 4 to 18 months of age at a dosage of 2.65 g/kg/day (containing 0.41 g/kg/day of rosmarinic acid). The impact was evaluated by behavioral tests and histological analyses and compared with APP23 mice to which Neumentix was not administered. The results showed that Neumentix administration increased the survival rate of APP23 mice and effectively reduced Aβ accumulation by enhancing its phagocytosis by microglial cells. These findings suggest that Neumentix is a potential natural nutritional treatment for improving the progression of AD.</div></div>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":"1863 ","pages":"Article 149752"},"PeriodicalIF":2.7,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute high glucose exposure impairs synaptosomal vesicle release activity.","authors":"Nadine Alshakhshir, Lucy He, Liqin Zhao","doi":"10.1016/j.brainres.2025.149751","DOIUrl":"https://doi.org/10.1016/j.brainres.2025.149751","url":null,"abstract":"<p><strong>Background: </strong>Increasing evidence indicates an association between Alzheimer's disease (AD) and diabetes. AD and diabetic brains share a hyperglycemic phenotype, making it a plausible mechanistic link between the two diseases. The vacuolar-type ATPase (V-ATPase) is essential for neurotransmitter concentration in synaptic vesicles and subsequent neuronal transmission. However, its role in AD pathogenesis is unclear.</p><p><strong>Objectives: </strong>We sought to examine whether acute hyperglycemic exposure would alter synaptic vesicular exocytosis and V-ATPase function in synaptosomes freshly extracted from wildtype mouse brains.</p><p><strong>Methods: </strong>Synaptic exocytosis was studied by analyzing the synaptosomal release of the fluorescent dye acridine orange (AO) and the neurotransmitter glutamate. Synaptic V-ATPase activity was assessed by measuring V-ATPase assembly using co-immunoprecipitation and V-ATPase-released phosphates.</p><p><strong>Results: </strong>Acute hyperglycemia reduced synaptic vesicular exocytosis as indicated by attenuated AO and glutamate release. Moreover, acute hyperglycemia reduced synaptic V-ATPase assembly but not V-ATPase-released phosphates.</p><p><strong>Conclusions: </strong>The present work demonstrates that hyperglycemia can impair synaptic vesicular exocytosis, partially by reducing V-ATPase assembly. We hypothesize that these molecular changes can be a shared mechanistic contributor to synaptic dysfunction in AD and diabetes. Further studies are needed to investigate the impact of chronic hyperglycemia and glycolytic metabolism on synaptic vesicular activity and V-ATPase function in animal models of AD and diabetes.</p>","PeriodicalId":9083,"journal":{"name":"Brain Research","volume":" ","pages":"149751"},"PeriodicalIF":2.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}